library(tidyverse)
library(janitor)
library(broom)
library(readxl)
library(jsonlite)
library(gprofiler2)
theme_set(theme_bw())
set.seed(666)gvc_agora_opentargets
Setup environment
Read and prep data
GVC
Genes within 1Mb window of (each side of?) GVC loci from Fanny:
gvc <- read_xlsx("GVC_1Mb_comparison_050224.xlsx") |>
clean_names() |>
separate(gene_id, c("gene_id", "version")) |>
select(-version, -agora_nominated_list, -opentarget_info)
gvcgvc.genes <- gvc |> distinct(gene_id, .keep_all = TRUE) |> select(gene_id, gene_symbol) |> arrange(gene_symbol)
gvc.genesAgora
Alzheimer’s disease gene prioritization scores from Agora:
ago <- read_json("syn25741025.overall_scores.json", simplifyVector = TRUE) |> as_tibble()
agoOpen Targets
Alzheimer’s disease gene prioritization scores from Open Targets:
ot <- read_tsv("OT-MONDO_0004975-associated-targets-6_4_2024-v24_03.tsv", show_col_types = FALSE, na = "No data")
otAdd Ensembl Gene IDs (WTF!):
otcols <- colnames(ot)
otensg <- gconvert(
query = ot$symbol,
organism = "hsapiens",
target= "ENSG",
mthreshold = Inf,
filter_na = TRUE) |>
mutate(input_number = as.character(input_number)) |>
left_join(ot |> rownames_to_column(var = "input_number"), by = "input_number") |>
select(ensembl_gene_id = target, otcols)
otensgAnnotate GVC genes with Agora and Open Targets scores
sum(gvc.genes$gene_id %in% ago$ensembl_gene_id)[1] 1212
sum(gvc.genes$gene_id %in% otensg$ensembl_gene_id)[1] 405
Arrange by Agora’s genetics_score and Open Targets’ otGeneticsPortal:
d1 <- gvc.genes |>
left_join(ago, by = join_by(gene_id == ensembl_gene_id)) |>
left_join(otensg, by = join_by(gene_id == ensembl_gene_id)) |>
arrange(desc(genetics_score), desc(otGeneticsPortal))
d1Perform ORA of GVC genes sorted by Agora and Open Targets genetics scores
query <- d1 |> distinct(symbol) |> pull(symbol)
gostres <- gost(query = query,
organism = "hsapiens",
domain_scope = "annotated",
exclude_iea = TRUE,
ordered_query = TRUE,
significant = TRUE,
user_threshold = 0.005,
correction_method = "fdr")
gostres$result |> select(term_name, term_id, source, everything())gostplot(gostres, capped = FALSE, interactive = TRUE)Perform correlation analysis of GVC genes using Agora and Open Targets scores
d1 |> nrow()[1] 1345
d1 |> drop_na(genetics_score, otGeneticsPortal) |> nrow()[1] 193
d1 |> drop_na(genetics_score, otGeneticsPortal) |>
summarize(cor = tidy(cor.test(genetics_score, otGeneticsPortal, method="kendall"))) |>
unnest(cor)d1 |> nrow()[1] 1345
d1 |> drop_na(target_risk_score, globalScore) |> nrow()[1] 399
d1 |> drop_na(target_risk_score, globalScore) |>
summarize(cor = tidy(cor.test(target_risk_score, globalScore, method="kendall"))) |>
unnest(cor)Overall correlation between Agora and Open Targets
d2 <- ago |>
left_join(otensg, by = "ensembl_gene_id") |>
arrange(desc(genetics_score), desc(otGeneticsPortal))
d2d2 |> nrow()[1] 24801
d2 |> drop_na(genetics_score, otGeneticsPortal) |> nrow()[1] 354
d2 |> drop_na(genetics_score, otGeneticsPortal) |>
summarize(cor = tidy(cor.test(genetics_score, otGeneticsPortal, method="kendall"))) |>
unnest(cor)d2 |> nrow()[1] 24801
d2 |> drop_na(target_risk_score, globalScore) |> nrow()[1] 4436
d2 |> drop_na(target_risk_score, globalScore) |>
summarize(cor = tidy(cor.test(target_risk_score, globalScore, method="kendall"))) |>
unnest(cor)Print environment
sessioninfo::session_info()─ Session info ───────────────────────────────────────────────────────────────
setting value
version R version 4.4.0 (2024-04-24)
os macOS Sonoma 14.5
system aarch64, darwin20
ui X11
language (EN)
collate en_US.UTF-8
ctype en_US.UTF-8
tz America/New_York
date 2024-06-04
pandoc 3.1.11 @ /Applications/RStudio.app/Contents/Resources/app/quarto/bin/tools/aarch64/ (via rmarkdown)
─ Packages ───────────────────────────────────────────────────────────────────
package * version date (UTC) lib source
backports 1.5.0 2024-05-23 [1] CRAN (R 4.4.0)
bit 4.0.5 2022-11-15 [1] CRAN (R 4.4.0)
bit64 4.0.5 2020-08-30 [1] CRAN (R 4.4.0)
bitops 1.0-7 2021-04-24 [1] CRAN (R 4.4.0)
broom * 1.0.6 2024-05-17 [1] CRAN (R 4.4.0)
cellranger 1.1.0 2016-07-27 [1] CRAN (R 4.4.0)
cli 3.6.2 2023-12-11 [1] CRAN (R 4.4.0)
colorspace 2.1-0 2023-01-23 [1] CRAN (R 4.4.0)
crayon 1.5.2 2022-09-29 [1] CRAN (R 4.4.0)
crosstalk 1.2.1 2023-11-23 [1] CRAN (R 4.4.0)
data.table 1.15.4 2024-03-30 [1] CRAN (R 4.4.0)
digest 0.6.35 2024-03-11 [1] CRAN (R 4.4.0)
dplyr * 1.1.4 2023-11-17 [1] CRAN (R 4.4.0)
evaluate 0.23 2023-11-01 [1] CRAN (R 4.4.0)
fansi 1.0.6 2023-12-08 [1] CRAN (R 4.4.0)
fastmap 1.2.0 2024-05-15 [1] CRAN (R 4.4.0)
forcats * 1.0.0 2023-01-29 [1] CRAN (R 4.4.0)
generics 0.1.3 2022-07-05 [1] CRAN (R 4.4.0)
ggplot2 * 3.5.1 2024-04-23 [1] CRAN (R 4.4.0)
glue 1.7.0 2024-01-09 [1] CRAN (R 4.4.0)
gprofiler2 * 0.2.3 2024-02-23 [1] CRAN (R 4.4.0)
gtable 0.3.5 2024-04-22 [1] CRAN (R 4.4.0)
hms 1.1.3 2023-03-21 [1] CRAN (R 4.4.0)
htmltools 0.5.8.1 2024-04-04 [1] CRAN (R 4.4.0)
htmlwidgets 1.6.4 2023-12-06 [1] CRAN (R 4.4.0)
httpuv 1.6.15 2024-03-26 [1] CRAN (R 4.4.0)
httr 1.4.7 2023-08-15 [1] CRAN (R 4.4.0)
janitor * 2.2.0 2023-02-02 [1] CRAN (R 4.4.0)
jsonlite * 1.8.8 2023-12-04 [1] CRAN (R 4.4.0)
knitr 1.47 2024-05-29 [1] CRAN (R 4.4.0)
labeling 0.4.3 2023-08-29 [1] CRAN (R 4.4.0)
later 1.3.2 2023-12-06 [1] CRAN (R 4.4.0)
lazyeval 0.2.2 2019-03-15 [1] CRAN (R 4.4.0)
lifecycle 1.0.4 2023-11-07 [1] CRAN (R 4.4.0)
lubridate * 1.9.3 2023-09-27 [1] CRAN (R 4.4.0)
magrittr 2.0.3 2022-03-30 [1] CRAN (R 4.4.0)
mime 0.12 2021-09-28 [1] CRAN (R 4.4.0)
munsell 0.5.1 2024-04-01 [1] CRAN (R 4.4.0)
pillar 1.9.0 2023-03-22 [1] CRAN (R 4.4.0)
pkgconfig 2.0.3 2019-09-22 [1] CRAN (R 4.4.0)
plotly 4.10.4 2024-01-13 [1] CRAN (R 4.4.0)
promises 1.3.0 2024-04-05 [1] CRAN (R 4.4.0)
purrr * 1.0.2 2023-08-10 [1] CRAN (R 4.4.0)
R6 2.5.1 2021-08-19 [1] CRAN (R 4.4.0)
Rcpp 1.0.12 2024-01-09 [1] CRAN (R 4.4.0)
RCurl 1.98-1.14 2024-01-09 [1] CRAN (R 4.4.0)
readr * 2.1.5 2024-01-10 [1] CRAN (R 4.4.0)
readxl * 1.4.3 2023-07-06 [1] CRAN (R 4.4.0)
rlang 1.1.3 2024-01-10 [1] CRAN (R 4.4.0)
rmarkdown 2.27 2024-05-17 [1] CRAN (R 4.4.0)
rstudioapi 0.16.0 2024-03-24 [1] CRAN (R 4.4.0)
scales 1.3.0 2023-11-28 [1] CRAN (R 4.4.0)
sessioninfo 1.2.2 2021-12-06 [1] CRAN (R 4.4.0)
shiny 1.8.1.1 2024-04-02 [1] CRAN (R 4.4.0)
snakecase 0.11.1 2023-08-27 [1] CRAN (R 4.4.0)
stringi 1.8.4 2024-05-06 [1] CRAN (R 4.4.0)
stringr * 1.5.1 2023-11-14 [1] CRAN (R 4.4.0)
tibble * 3.2.1 2023-03-20 [1] CRAN (R 4.4.0)
tidyr * 1.3.1 2024-01-24 [1] CRAN (R 4.4.0)
tidyselect 1.2.1 2024-03-11 [1] CRAN (R 4.4.0)
tidyverse * 2.0.0 2023-02-22 [1] CRAN (R 4.4.0)
timechange 0.3.0 2024-01-18 [1] CRAN (R 4.4.0)
tzdb 0.4.0 2023-05-12 [1] CRAN (R 4.4.0)
utf8 1.2.4 2023-10-22 [1] CRAN (R 4.4.0)
vctrs 0.6.5 2023-12-01 [1] CRAN (R 4.4.0)
viridisLite 0.4.2 2023-05-02 [1] CRAN (R 4.4.0)
vroom 1.6.5 2023-12-05 [1] CRAN (R 4.4.0)
withr 3.0.0 2024-01-16 [1] CRAN (R 4.4.0)
xfun 0.44 2024-05-15 [1] CRAN (R 4.4.0)
xtable 1.8-4 2019-04-21 [1] CRAN (R 4.4.0)
yaml 2.3.8 2023-12-11 [1] CRAN (R 4.4.0)
[1] /Library/Frameworks/R.framework/Versions/4.4-arm64/Resources/library
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